CAR-T is a new type of cancer immunotherapy, which extracts immune cells with the potential to attack cancer from the patient, and makes them have the “eyes” targeting cancer cells through in vitro transformation, and then transfuses back into the patient to identify and kill tumor cells carrying targets specifically.
The treatment effect of CAR-T for leukemia therapy is amazing
B cell is a kind of immune cell in the human body to help resist external infection. When it begins to undergo malignant transformation for disordered proliferation in vivo, it becomes B cell leukemia. Fortunately, B cell s have a class of specific identification that all other organizations do not express: CD19 (a kind of antigen protein expressing on a variety of hematologic malignancies cell surface, including B cell lymphoma and leukemia cells), which provides an ideal target for the treatment of CAR-T.
In a few cases before, there had achieved remarkable curative effect that the existing treatments are not response of patients with advanced cancer. In 2016, on the American Society Hematology annual meeting, Novartis, Juno and Kite, three CAR-T treatment leaders, reported the latest treatment results of clinical trials of targeted CD19 CAR-T. Thankfully, more patients reproduce those early inspiring results:
In the experiment of Novartis and Juno, nearly 90% of the patients’ leukemic cells were almost completely removed. Clinical trials of Kite company also achieved complete remission in 60%. The first beneficiary from this kind of therapy were already living without disease for more than 3 years.
The effect of CAR-T for lyphoma therapy is powerful and lasting
In March, 2017, Kite Pharma issued the clinical trial results about CD19 targeting CAR-T cells for relapsed and refractory non Hodgkin's lymphoma (NHL).
In this study, after 22 patients with relapsed/refractory NHL received Flu/Cy conditioning regimen in low dose, then they received a single dose of anti CD19 CAR-T cells therapy. 16 (73%) of 22 patients achieved objective response (OR), 12 (55%) reached complete remission (CR).
In all patients with invasive B cells NHL (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, transformed follicular lymphoma), the final OR and CR ratio were 68% and 47%. The follow-up after treatment of 7-24 months found that in 12 of the patients who achieved CR, 11 patients were still in continuous CR state. 12 patients (55%) had 3-4 reversible neurotoxicity symptoms, including confusion, dysphagia, encephalopathy and ataxia.
How does CAR-T meet greater challenges
For CART-19 clinical results, whether from foreign or domestic, the recurrence of the problem was inevitable. There were many reasons for recurrence, tumor antigen loss, persistent CAR-T or the source of scFv. But we found that CAR-T cells in vivo constancy and clinical response had a direct correlation.
For the time being, CAR-T's strengths are concentrated at two points:
The attack on the target is very specific;
Cancer cells with targets can be completely removed in the long-term.
But the more widely applications from CAR-T are limited precisely by the two characteristics of their own:
Because of the heterogeneity of the tumor, it is difficult to find a widely expressed target like CD19 in most other cancers, so even with CAR-T, it is difficult to remove the cancer burden effectively;
Many so-called cancer specific targets, in fact, are also expressed in varying degrees by normal tissues, so the use of CAR-T for attacks may cause negligible side effects on normal human tissues.
About the author:
Creative Biolabs has built itself CellRapeutics™ CAR platform for Leukemia and Lymphoma therapy.
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